Rabies virus infection of cultured adult mouse dorsal root ganglion neurons

Castellanos, Jaime E.; Hurtado, Hernán; Arias, Janeth; Velandia, Alvaro

doi:10.1590/s0074-02761996000500014

Cited by 10 publications

(1 citation statement)

References 22 publications

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“…A pair of mice (strain ICR) were injected in the posterior right footpad, the first with 30 μl of the viral inoculum (CVS strain, 10 6.7 DL 50 ) obtained in mouse brain diluted in DMEM supplemented with 2 % fetal calf serum (FCS; Castellanos et al 1996), and the second was injected with a 10 % brain homogenate in DMEM supplemented with 2 % FCS (mock), which was used for the controls. The procedure was repeated three times.…”

Section: Infection With Rabvmentioning

confidence: 99%

In vivo differential susceptibility of sensory neurons to rabies virus infection

2013

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There is controversy with regard to the entry pathway of the rabies virus (RABV) into the central nervous system (CNS). Some authors have suggested that the virus inoculated at the periphery is captured and transported to CNS only by motor neurons; however, it has been reported that dorsal root ganglia (DRG) sensory neurons capture and transport the virus to the spinal cord (SC) and then to the brain. It is probable that preferences for one pathway or another depend on the site of inoculation and the post-infection time. Therefore, in the present study, we evaluated different vertebral segments and post-infection times, along with the location, number, and subpopulation of sensory neurons susceptible to infection after inoculating RABV in the footpads of adult mice. It was noted that the virus inoculated in the footpad preferentially entered the CNS through the large-sized DRG sensory neurons, while infection of the motor neurons occurred later. Further, it was found that the virus was dispersed in spinal cord trans-synaptically through the interneurons, arriving at both sensory neurons and contralateral motor neurons. In conclusion, we observed that RABV inoculated in the plantar footpad is captured preferentially by large sensory neurons and is transported to the DRG, where it replicates and is spread to the SC using transynaptic jumps, infecting sensory and motor neurons at the same level before ascending to the brain.

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Section: Infection With Rabvmentioning

confidence: 99%

In vivo differential susceptibility of sensory neurons to rabies virus infection

2013

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Morphological and biochemical characterisation of sensory neurons infected in vitro with rabies virus

Martínez-Gutiérrez

Castellanos

2007

Acta Neuropathol

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This work was aimed at the morphological and biochemical characterisation of the most susceptible neuronal subpopulation to rabies virus (RABV) infection. Adult mouse DRG cultures were infected with RABV and double-processed for viral antigen detection and neuropeptides: calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). It was found that 56% of the neurons in culture were small (diameter < 20 microm) but, in spite of this, 69% of the infected neurons had intermediate and large diameters (> or = 20 microm). More than 50% of infected neurons expressed NPY, VIP or SP, whereas no association was found between infected neurons and the presence of CGRP or GAL. Despite SP having been shown to be a small neuron marker, it was found that RABV infects medium and large-sized SP positive cells. RABV preference for larger neurons could explain part of the neuropathogenesis since it can be suggested that, following a rabid accident, the virus uses large neurons (mainly innervating muscle and joints) in vivo to be transported later on to the central nervous system.

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Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice

2009

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The involvement of dorsal root ganglia was studied in an in vivo model of experimental rabies virus infection using the challenge virus standard (CVS-11) strain. Dorsal root ganglia neurons infected with CVS in vitro show prolonged survival and few morphological changes, and are commonly used to study the infection. It has been established that after peripheral inoculation of mice with CVS the brain and spinal cord show relatively few neurodegenerative changes, but detailed studies of pathological changes in dorsal root ganglia have not previously been performed in this in vivo experimental model. In this study, adult ICR mice were inoculated in the right hindlimb footpad with CVS. Spinal cords and dorsal root ganglia were evaluated at serial time points for histopathological and ultrastructural changes and for biochemical markers of cell death. Light microscopy showed multifocal mononuclear inflammatory cell infiltrates in the sensory ganglia and a spectrum of degenerative neuronal changes. Ultrastructural changes in gangliocytes included features characteristic of the axotomy response, the appearance of numerous autophagic compartments, and aggregation of intermediate filaments, while the neurons retained relatively intact mitochondria and plasma membranes. Later in the process, there were more extensive degenerative neuronal changes without typical features of either apoptosis or necrosis. The degree of degenerative neuronal changes in gangliocytes contrasts with observations in CNS neurons in experimental rabies. Hence, gangliocytes exhibit selective vulnerability in this animal model. This contrasts markedly with the fact that they are, unlike CNS neurons, highly permissive to CVS infection in vitro. Further study is needed to determine mechanisms for this selective vulnerability, which will give us a better understanding of the pathogenesis of rabies.

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Rabies virus infection of cultured adult mouse dorsal root ganglion neurons

Cited by 10 publications

References 22 publications

In vivo differential susceptibility of sensory neurons to rabies virus infection

In vivo differential susceptibility of sensory neurons to rabies virus infection

Morphological and biochemical characterisation of sensory neurons infected in vitro with rabies virus

Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice

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